posted on 2016-01-14, 00:00authored bySameer Agarwal, Amit Patil, Umesh Aware, Prashant Deshmukh, Brijesh Darji, Santosh Sasane, Kalapatapu V. V.
M. Sairam, Priyanka Priyadarsiny, Poonam Giri, Harilal Patel, Suresh Giri, Mukul Jain, Ranjit C. Desai
TGR5
is a G protein-coupled receptor (GPCR), activation of which promotes
secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin
secretion. The 2-thio-imidazole derivative 6g was identified
as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile.
The compound 6g was found to have potent glucose lowering
effects in vivo during an oral glucose tolerance
test in DIO C57 mice with ED50 of 7.9 mg/kg and ED90 of 29.2 mg/kg.